Two cell line models to study multiorganic metastasis and immunotherapy in lung squamous cell carcinoma
Fecha
2022Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Impacto
|
10.1242/dmm.049137
Resumen
There is a paucity of adequate mouse models and cell lines available to study lung squamous cell carcinoma (LUSC). We have generated and characterized two models of phenotypically different transplantable LUSC cell lines, i.e. UN-SCC679 and UN-SCC680, derived from A/J mice that had been chemically induced with N-nitroso-tris-chloroethylurea (NTCU). Furthermore, we genetically characterized and co ...
[++]
There is a paucity of adequate mouse models and cell lines available to study lung squamous cell carcinoma (LUSC). We have generated and characterized two models of phenotypically different transplantable LUSC cell lines, i.e. UN-SCC679 and UN-SCC680, derived from A/J mice that had been chemically induced with N-nitroso-tris-chloroethylurea (NTCU). Furthermore, we genetically characterized and compared both LUSC cell lines by performing whole-exome and RNA sequencing. These experiments revealed similar genetic and transcriptomic patterns that may correspond to the classic LUSC human subtype. In addition, we compared the immune landscape generated by both tumor cells lines in vivo and assessed their response to immune checkpoint inhibition. The differences between the two cell lines are a good model for the remarkable heterogeneity of human squamous cell carcinoma. Study of the metastatic potential of these models revealed that both cell lines represent the organotropism of LUSC in humans, i.e. affinity to the brain, bones, liver and adrenal glands. In summary, we have generated valuable cell line tools for LUSC research, which recapitulates the complexity of the human disease. [--]
Materias
Lung cancer,
Squamous,
NTCU-mouse model,
Syngeneic cell lines,
RNASeq,
Immunotherapy
Editor
The Company of Biologists
Publicado en
Disease Models & Mechanisms, (2022) 15, dmm049137
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
This work was supported by FIMA, Centro de Investigacion Biomedica en Red de Cancer (CIBERONC) (grant number: CB16/12/00443), Fundacion Cientifica Asociacion Espanola Contra el Cancer (grant number: GCB14-2170), Fundacion Ramon Areces, Instituto de Salud Carlos III and the European Regional Development Fund (ERDF, A way to make Europe) (grant numbers: PI19/00098; PI19/00230; PI20/00419), Fundacion Roberto Arnal Planelles and an IASLC Fellowship funding (K.V.); D.S. was supported by the Juan de la Cierva-Incorporacion program, Spanish Ministry of Science and Innovation (grant number: IJCI-2016-27595); E.R. was supported by a FPU, Spanish Ministry of Education ( grant number: FPU17/01168); M.E. was supported by PFIS, Spanish Ministry of Health, M.L. was supported by a Junior Investigator grant from AECC.